In-silico and in-vitro evaluation of anti-oxidant and anti-hypertensive activities of Chenopodium ambrosoides LINN. ethanol leaf extract

Oxidative stress and free radicals have been implicated in ethno-pathogenesis of hypertension and cardiovascular disease. C. ambrosoides Linn. is a popular plant used in the management of oxidative stress related diseases such as hypertension and obesity in Nigeria and West African countries; however, studies validating the antioxidant and antihypertensive potential of this plant is scanty in literature. Thus, this study was designed to investigate the antioxidant and antihypertensive activities of C. ambrosoides ethanolic leaf extract using in-vitro (vis-a-vis) DPPH free radical scavenging assay, nitric oxide radical inhibition assay, lipid peroxidation inhibition assay, ferric reducing power assay and angiotensin converting enzyme inhibition assay) and in-silico (Molecular docking) techniques and results analyzed using GraphPad prism8 software and Multiple test as criteria for statistical comparison and significance. Gas chromatography mass spectrometry (GCMS) analysis was employed to identify constituent bioactive compounds in the extract. The results of the in-vitro anti-oxidants assays show dose dependent inhibition with the highest activity observed at 2.5 mg/ml. The ferric reducing power activity of the extract significantly (P<0.05) shows higher activity than the ascorbic acid standard at all concentration with the highest activity observed at 2.5mg/ml (77.030% against 69.159%). The extract significantly scavenged DPPH radical than ascorbic acid standard at 2.5mg/ml (81.161% against 75.378%), however at low concentration (1.5mg/ml-0.5mg/ml) the standard shows higher activity than the extract, however dose dependence was maintained. Ascorbic acid standard significantly shows higher activity than the extracts lipid peroxidation inhibition and nitric oxide inhibition activity at all concentration. The extract exhibited high angiotensin converting enzyme (ACE) inhibited in a dose dependent manner with the highest activity at 2.5mg/ml (95.990%). The ACE inhibitory potential of C. ambrosoides extract was corroborated by in-silico studies which revealed that 14 out of the 96 identified bioactive compounds through GCMS exhibited higher negative binding affinities than lisinopril (-6.8 Kcal/mol), with the compound 2,4-Diamino-6,8-bis[3,4-dichlorophenyl]-5,6-dihydro-8H-thiapyrano[4,34,5]thieno[2,3d]pyrimidine having the highest binding affinity (-8.0Kcal/mol) In conclusion, it is suggested that the anti-hypertensive activity demonstrated by C. ambrosoides might be mediated via its anti-oxidant ability and ACE inhibitory potential.